Brexpiprazole/Sertraline Combo Shows Benefits for PTSD Symptoms
In post-traumatic stress disorder (PTSD), brexpiprazole in combination with sertraline was associated with greater improvements in symptom severity and functioning compared to sertraline in combination with placebo across symptom clusters. Results from the pooled post hoc analysis were presented via poster at the 2025 Psych Congress.
PTSD symptoms can be characterized into 4 clusters: intrusion, avoidance, negative cognitions/mood, and arousal/reactivity.
The study examined brexpiprazole plus sertraline versus sertraline plus placebo for PTSD symptom clusters using data from 3 trials conducted in adults, based on the Clinician-Administered PTSD Scale for DSM-5 (CAP-5). CAP-5 symptom cluster data was analyzed across 3 different pools: all 3 trials together, the 2 flexible-dose trials, and the 2 Phase 3 trials. The primary endpoint from the 3 trials was change from Week 1 to Week 10 in CAPS-5 total score.
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In all 3 pools for the present study, researchers compared the least squares (LS) mean change in each CAPS-5 symptom cluster score for both brexpiprazole plus sertraline and sertraline plus placebo. Analyses used a mixed model for repeated measures without adjustment for multiplicity. P-values were nominal.
Across the pools (All, n=820; Flexible-dose, n=434; Phase 3, n=668), LS mean change from Week 1 to Week 10 in CAPS-5 Intrusion score ranged from –5.04 to –5.11 for brexpiprazole plus sertraline, and –3.22 to –4.23 for sertraline plus placebo (Week 10 comparison: All, P=0.0002; Flexible-dose, P < 0.0001; Phase 3, P=0.017). LS mean change in Avoidance score was–2.14 to –2.21 for brexpiprazole plus sertraline, and –1.45 to –1.89 for sertraline plus placebo (All, P=0.015; Flexible-dose, P=0.0015; Phase 3, P=0.18). LS mean change in Negative cognitions and mood score was, –6.82 to –6.95 for brexpiprazole plus sertraline and –4.98 to –5.98 for sertraline plus placebo (All, P=0.0037; Flexible-dose, P=0.0011; Phase 3, P=0.037). LS mean change in Arousal and reactivity score was, –3.83 to –4.06 for brexpiprazole plus sertraline and –2.87 to –3.23 for sertraline plus placebo (All, P=0.0095; Flexible-dose, P=0.0088; Phase 3, P=0.0076).
This study was sponsored by Otsuka Pharmaceutical Development & Commercialization, Inc., and H. Lundbeck A/S.
References
American Psychiatric Association. Posttraumatic stress disorder. 2013. Accessed October 15, 2025. https://www.psychiatry.org/file%20library/psychiatrists/practice/dsm/apa_dsm-5-ptsd.pdf
Bevernage B, at al. Effect of brexpiprazole in combination with sertraline on post-traumatic stress disorder symptom clusters: intrusion, avoidance, negative cognitions/mood, and arousal/reactivity. Poster presented at Psych Congress; September 17-21, 2025; San Diego, California.
